What are the other Names for this Condition? (Also known as/Synonyms)

• Esophageal Gastrointestinal Stromal Tumor
• GIST of Esophagus
• Oesophageal Gastrointestinal Stromal Tumor

What is Gastrointestinal Stromal Tumor of Esophagus? (Definition/Background Information)

• A gastrointestinal stromal tumor (GIST) is a type of tumor that occurs in the gastrointestinal tract. It can either be benign or malignant, depending on various characteristics. Most tumors occur randomly, while some originate due to a family history of the condition
• The most common location of this tumor is the stomach or small intestine. The origin of the tumor is uncertain. Some researchers believe that these tumors originate from a special type of cells that are present in the gastrointestinal tract, called the interstitial cells of Cajal (ICCs)
• Gastrointestinal Stromal Tumor of Esophagus is a very rare tumor that forms in the esophagus. The esophagus is a part of the upper gastrointestinal tract and is also known as the ‘food-pipe’
• Gastrointestinal Stromal Tumor of Esophagus may arise sporadically, or in the presence of an associated genetic disorder, such as neurofibromatosis type 1, Carney triad, or Carney-Stratakis syndrome. In a majority though, the involvement of KIT and PDGFRA genes are noted (for both sporadic and familial cases)
• Small-sized tumors are not known to cause any significant symptoms, but larger tumors may cause to swallowing difficulties due to obstruction of food-pipe. Malignant tumors are known to metastasize to the stomach, lungs, and other distant regions
• The standard treatment approach involves a surgical excision and removal of the entire tumor followed by chemotherapy. However, Gastrointestinal Stromal Tumor of Esophagus outcome depends on the type of tumor (whether benign or malignant) and whether it has metastasized

Who gets Gastrointestinal Stromal Tumor of Esophagus? (Age and Sex Distribution)

• Gastrointestinal Stromal Tumor of Esophagus constitute about 3% of all GIST tumors
• The tumor is mostly observed in middle to older adults in the 50-65 years’ age group. In rare cases, it may be seen in children too
• Both males and females are affected and no specific preference for any gender is observed
• When the tumor is seen among younger populations, it may be seen in the background of an underlying genetic disorder. In such cases, females are affected more than males
• No racial or ethnic predilection is also noted

What are the Risk Factors for Gastrointestinal Stromal Tumor of Esophagus? (Predisposing Factors)

• Currently, no definitive risk factors for Gastrointestinal Stromal Tumor of Esophagus are known, when the tumors occur sporadically
• However, in some cases, an association of the tumor with the following genetic disorders is noted:
  • Neurofibromatosis type 1 (NF1)
  • Carney triad
  • Carney-Stratakis syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gastrointestinal Stromal Tumor of Esophagus? (Etiology)

The cause of Gastrointestinal Stromal Tumors of Esophagus is due to genetic mutations.

• Mutations in two specific genes account for a majority of the cases. Mutation in these genes result in an uncontrolled growth of cells, leading to tumor formation
• It is estimated that 80% of such tumors are caused by a mutation in the KIT gene; around 10% of the diagnosed cases are caused by a mutation in the PDGFRA gene. The reminder of the tumors occur due to mutation in certain other genes

There are two types of gastrointestinal stromal tumors (GISTs) - sporadic tumors and familial tumors.

• Both, familial and sporadic tumors are caused by mutations in the KIT and PDGFRA genes. These genes are responsible for making proteins that are involved in cell growth and cell death. In a minority of the cases, the mutations are inherited from parents and in such cases, the tumors are called familial GISTs
• In familial GIST, mutations are inherited in an autosomal dominant pattern, which means that only one copy of the mutated gene in each cell is enough to increase an individual’s chance of developing gastrointestinal stromal tumors
• In sporadic cases of GIST, there is usually a single tumor; whereas in the familial type, multiple GIST tumors may occur

What are the Signs and Symptoms of Gastrointestinal Stromal Tumor of Esophagus?

Some small-sized Gastrointestinal Stromal Tumors of Esophagus may not cause any significant symptoms and are detected incidentally. In others, the following signs and symptoms may be noted:

• Most common symptom is swallowing difficulty from large-sized tumors
• The tumors are usually located nearer to the stomach and esophagogastric junction. They may be also found occasionally in the mediastinal region
• Most tumors are 1-3 cm sized nodules on the esophageal wall, or located deeper into the wall layers; some may grow to about 5 cm in size
• The tumors are commonly located in the middle-third or lower-third portion of the esophagus, closer to the stomach
• In a majority of the cases, solitary tumors are observed; while, in familial cases, there may be multiple tumors (including tumors at other body locations)
• Malignant tumors may lead to weight loss, anemia (due to bleeding), pain in the upper abdominal region, and skin discoloration

Urticaria pigmentosa (a skin disorder) is known to occur in patients with GISTs. In this disorder, the individual has skin lesions that are characterized by raised patches of itchy brownish skin. These may be either localized (confined to certain parts of the body), or present all over the body.

How is Gastrointestinal Stromal Tumor of the Esophagus Diagnosed?

A diagnosis of Gastrointestinal Stromal Tumor of Esophagus would involve:

• A thorough medical history and physical examination
• X-ray of the chest
• CT or MRI scan of the chest: For advanced cases and to check cancer growth and spread, including lymph node involvement
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is good technique for tumor detection including tumor invasion parameters, and whether nearby lymph nodes are affected
• Endocytoscopy: It is a non-invasive technique helpful for invasive carcinomas that are located superficially
• Early cancer lesions may be detected using narrow band imaging technique
• Barium swallow
• Whole body PET scans to determine how far the cancer has spread to other organ systems

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include:

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor and the tumor may be misdiagnosed. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor
• Open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note: Esophageal GIST is known to closely resemble leiomyoma of esophagus, a benign tumor, on imaging studies; it is generally difficult to differentiate between the two tumors.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gastrointestinal Stromal Tumor of Esophagus?

Gastrointestinal Stromal Tumor of Esophagus may cause the following complications:

• Ulceration of the tumor can lead to secondary infections of bacteria and fungus

• Large-sized tumors may cause hemorrhaging of the gastrointestinal tract and perforation of bowel
• Compression of the underlying nerve, which can affect nerve function
• Severe obstruction of the food-pipe with pain, leading to difficulties in eating
• Stricture formation of esophagus
• Tumor metastasis to local and distant regions including to the lymph nodes, stomach, intestines, lungs, liver, and other areas of the abdominal cavity
• Complications that arise from any underlying genetic disorder
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication
• High risk of tumor recurrence after surgery have been reported in aggressive tumors

How is Gastrointestinal Stromal Tumor of Esophagus Treated?

Treatment measures of Gastrointestinal Stromal Tumor of Esophagus include:

• Wide surgical excision of GIST with removal of the entire lesion, which is followed by a course of chemotherapy is the standard treatment employed. The surgical excision may be performed using laparoscopic surgical techniques
• Non-surgical intervention includes chemotherapy and/or radiotherapy - these modalities are generally used to shrink the tumor, if possible, before an invasive surgical procedure is planned and performed
• Arterial or chemo-embolization is used to provide temporary relief from the symptoms, and reduce blood loss during a surgical procedure
• Post-operative care is important: A minimum activity level is to be ensured, until the surgical wound heals
• Follow-up care with regular screening and check-ups are important and recommended

How can Gastrointestinal Stromal Tumor of Esophagus be Prevented?

Currently, no known preventive methods exist for Gastrointestinal Stromal Tumor of Esophagus. However, in case it is associated with a genetic disorder, then the following may be considered:

• Genetic counseling and testing
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already endured the tumor, due to its high metastasizing potential and possibility of recurrence. Often several years of active vigilance is necessary.

What is the Prognosis of Gastrointestinal Stromal Tumor of Esophagus? (Outcomes/Resolutions)

The prognosis for individuals with Gastrointestinal Stromal Tumor of Esophagus depends on whether the tumor is benign or malignant.

• The prognosis is generally excellent for benign tumors following their surgical excision
• However, the prognosis of malignant GIST tumors may depend on a set of factors that include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease may have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment; good response to treatment (surgery and/or chemotherapy/radiation therapy)
  • Progression of the condition makes the outcome worse
• Generally, the prognosis of malignant GIST is variable. Some are known to metastasize early and can lead to death in a few years; while others may take several years to spread to other sites. In rare cases, when malignant tumors are seen in the mediastinal region, they are reported to show a much better prognosis
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment

Additional and Relevant Useful Information for Gastrointestinal Stromal Tumor of Esophagus:

The following DoveMed website links are useful resources for additional information:

http://www.dovemed.com/diseases-conditions/cancer/